ω-Aryl-13,14-didehydro-interphenylene-PGA compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 776,552,filed Mar. 7, 1977; which is a divisional application of Ser. No.657,739, filed Feb. 13, 1976, issued as U.S. Pat. No. 4,029,681 on June14, 1977.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 657,739, filed Feb. 13, 1976, now issued asU.S. Pat. No. 4,029,681.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## WHEREIN D is##STR2## wherein Y₁ is --C.tbd.C--; wherein Z₅ is ##STR3## WHEREIN G ISONE, 2, OR 3; WHEREIN Z₃ is oxa or methylene;Wherein T is chloro;fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, oralkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3,the various T's being the same or different, with the proviso that notmore than two T's are other than alkyl; Wherein M₁ is ##STR4## whereinR₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆is methyl only when the other is hydrogen; Wherein L₁ is ##STR5## or amixture of ##STR6## wherein R₃ and R₄ are hydrogen, methyl, or fluoro,being the same or different, with the proviso that one of R₃ and R₄ isfluoro only when the other is hydrogen or fluoro and Z₃ is methylene;and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substituted with one, two, or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 2. A compound according to claim 1wherein D is ##STR7##
 3. A compound according to claim 1 wherein D is##STR8##
 4. A compound according to claim 3 wherein Z₃ is methylene. 5.A compound according to claim 4 wherein s is zero or one and T ischloro, fluoro, or trifluoromethyl.
 6. A compound according to claim 3wherein Z₃ is oxa.
 7. A compound according to claim 6 wherein s is zero.8. A compound according to claim 6 wherein s is zero or one and T ischloro, fluoro, or trifluoromethyl.
 9. A compound according to claim 8wherein Z₁ is ##STR9##
 10. A compound according to claim 8 wherein Z₁ is##STR10##
 11. A compound according to claim 8 wherein M₁ is ##STR11##12. A compound according to claim 11 wherein g is one.
 13. A compoundaccording to claim 12 wherein R₃, R₄, R₅, and R₆ are all hydrogen. 14.15-epi-3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-13,14-didehydro-PGA₁,methyl ester, a compound according to claim
 13. 15. A compound accordingto claim 13, wherein M₁ is ##STR12##
 16. A compound according to claim15, wherein g is three.
 17. A compound according to claim 15, wherein gis one.
 18. A compound according to claim 17, wherein R₃ and R₄ are bothhydrogen.
 19. A compound according to claim 18 wherein R₅ is methyl. 20.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-15-methyl-13,14-didehydro-PGA₁,a compound according to claim 19.21.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-15-methyl-13,14-didehydro-PGA₁,methyl ester, a compound according to claim
 19. 22. A compound accordingto claim 18 wherein R₆ is methyl. 23.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-13,14-didehydro-PGA₁,15-methyl ether, a compound according to claim
 22. 24.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-13,14-didehydro-PGA₁,methyl ester, 15-methyl ether, a compound according to claim
 22. 25. Acompound according to claim 18, wherein R₅ and R₆ are both hydrogen. 26.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-13,14-didehydro-PGA₁,a compound according to claim
 25. 27.3,7-Inter-m-phenylene-3-oxa-4,5,6,17,18,19,20-heptanor-16-phenoxy-13,14-didehydro-PGA₁,methyl ester, a compound according to claim
 25. 28. A compound accordingto claim 17, wherein at least one of R₃ and R₄ is methyl.
 29. A compoundaccording to claim 28, wherein R₃ and R₄ are both methyl.
 30. A compoundaccording to claim 29, wherein R₅ is methyl. 31.3,7-Inter-m-phenylene-3-oxa-4,5,6,18,19,20-hexanor-16-phenoxy-15,16-dimethyl-13,14-didehydro-PGA₁,methyl ester, a compound according to claim
 30. 32. A compound accordingto claim 29, wherein R₆ is methyl. 33.3,7-Inter-m-phenylene-3-oxa-4,5,6,18,19,20-hexanor-16-phenoxy-16-methyl-13,14-didehydro-PGA₁,methyl ester, 15-methyl ether, a compound according to claim
 32. 34. Acompound according to claim 29, wherein R₅ and R₆ are both hydrogen. 35.3,7-Inter-m-phenylene-3-oxa-4,5,6,18,19,20-hexanor-16-phenoxy-16-methyl-13,14-didehydro-PGA₁,a compound according to claim
 34. 36.3,7-Inter-m-phenylene-3-oxa-4,5,6,18,19,20-hexanor-16-phenoxy-16-methyl-13,14-didehydro-PGA₁,methyl ester, a compound according to claim 34.